Because of the biocompatibility of poly(alkyleneglycols), also known as polyalkyl ethers or poly(alkylene oxide), poly(oxyalkylene)-containing polymers can find use in various fields, in particular in biomedical fields, such as, for example, carriers for drug-delivery, artificial tissues, dentifrices, contact lenses, intraocular lenses, and other biomedical devices. (For a recent review of applications see the ACS Symposium Series 680, “Poly(ethyleneglycol): Chemistry and Biological Applications”, 1997, Harris and Zalipsky, eds.) However, poly(oxyalkylene)-containing polymers may be susceptible to degradation, in particular, oxidative degradation of its poly(oxyalkylene) chains under aerobic conditions. Oxidative degradation may cause changes in the properties of an article made from the poly(oxyalkylene)-containing polymers and limit the applications of poly(oxyalkylene)-containing polymers.
Susceptibility to oxidative degradation of a poly(oxyalkylene)-containing polymer can be effected by the method used in preparation and purification, post-manufacturing process (e.g., sterilization with autoclave, or the like), storage, and use. It is generally believed that, under aerobic conditions, a poly(oxyalkylene)-containing polymer may be degraded according to the mechanism of a free-radical chain reaction involving an oxidation step (see “Stability of the Polyoxyethylene Chain”, Donbrow, Max. Surfactant Sci. Ser. (1987), 23 (Nonionic Surfactants), 1011-1072, and references contained therein). First, homolytic degradation of the alkylene glycol chain in a poly(oxyalkylene)-containing polymer is initiated photochemically, thermally, or chemically (e.g., by actinic radiation including UV radiation, ionizing radiation, or microwave, at elevated temperatures, or with free-radical initiators, etc.), producing an alkylene glycol radical. This radical undergoes spontaneous oxidation under aerobic conditions to form peroxides and hydroperoxides. The resulting peroxides and hydroperoxides may then undergo a variety of subsequent reactions to yield by-products such as formic acid, lower alcohols, and the like. For a contact lens made from a poly(oxyalkylene)-containing polymer, the poly(oxyalkylene) chain of the poly(oxyalkylene)-containing polymer may be susceptible to oxidative degradation, leading to formation of by-products such as formic acid and others. These by-products, especially formic acid which can have irritating effects, are not desirable, and thus need to be eliminated or minimized. Moreover, a medical device made from a poly(oxyalkylene)-containing polymer may have a shorter shelf life because of oxidative degradation of the poly(oxyalkylene)-containing polymer.
There have been attempts to stabilize poly(oxyalkylene)-containing materials used for medical devices by using antioxidants. For example, see U.S. Pat. Nos. 5,290,585, 5,160,790, 5,179,186, 5,367,001, 4,886,866 and 5,175,229, and EP 0333899B1. The antioxidants disclosed in those patents are hindered phenolic compounds, such as butylated hydroxytoluene, tris (3,5-di-t-butyl-4hydroxy benzyl) isocyanurate, 2,2′-methylenebis (4-methyl-6-t-lutyl phenol), 1,3,5-Trimethyl-2,4,6-tris (3,5-di-t-butyl-4-hydroxybenzyl) benzene, octadecyl 3,5, di-t-butyl-4hydroxyhydrocinnamate, 4,4 methylenebis (2,6-di-t-butylphenol), p,p-dioctyl diphenylamine, 1,1,3-tris-(2-methyl-4-hydroxy-5-t-butylphenyl) butane, Irganox (Ciba Geigy), and Santonox (Monsanto Corp.). However, there are some disadvantages associated with those antioxidants in the prior art for stabilizing poly(oxyalkylene)-containing materials. Those antioxidants may not be suitable for applications where the device is remain in contact with living tissues for long periods of times due to their cytotoxicity, or are water insoluble so that they can not be used in a water-base formulation for making the poly(oxyalkylene)-containing materials. Furthermore, those antioxidants may not be efficient in stabilizing poly(oxyalkylene)-containing materials and/or reducing the levels of by-products such as formic acid, in case where the poly(oxyalkylene)-containing materials are used to make contact lenses or other medical devices.
Accordingly, there is still a need for a method for stabilizing poly(oxyalkylene)-containing polymeric materials using a biocompatible material. Such stabilized poly(oxyalkylene)-containing polymeric materials can find particular use in making a medical device which are in contact with living cells or tissues.